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Automatic Bi-level Positive Airway Pressure Delivery with Flow-Directed Pressure Modulation
and Expiratory Pressure Relief – an In-laboratory Comparison with Conventional Bi-level Positive
Airway Pressure Therapy
Paul Wylie, MD1 , Sukhdev Grover, MD2
1
Arkansas Center for Sleep Medicine, Little Rock AR;
2
Sleep Center of Greater Pittsburgh, Pittsburgh, PA
Study Objectives: To evaluate the therapeutic effect of Automatic
Bi-level Positive Airway Pressure with flow-matching and early
expiratory pressure relief (BiPAP® Auto with Bi-Flex®) to treat adult
obstructive sleep apnea/hypopnea. The study also evaluated the
therapeutic efficacy of BiPAP Auto with Bi-Flex as compared to
manually titrated conventional Bi-level Positive Pressure Therapy for
reduction of the Apnea/Hypopnea Index in adult OSAH patients, and
the “optimum” therapeutic pressures derived from the night therapy.
Study Design: Prospective cross-over, blinded analysis.
Setting: Sleep disorders center (Arkansas Center for Sleep Medicine,
Little Rock AR, Sleep Center of Greater Pittsburgh, Pittsburgh, PA).
Measurements and Results: Three nights of in-laboratory full
polysomnography were performed, using conventional bi-level therapy
being manually titrated, BiPAP set at therapeutic pressure levels,
BiPAP Auto with Bi-Flex set at operational pressure ranges.
Conclusions: The BiPAP Auto with Bi-Flex adequately treats OSAH,
provides a 90% pressure that is comparable to the ‘fixed’ pressure
level derived during manually titrated conventional bi-level therapy.
Abbreviations: BiPAP – Bi-level Positive Airway Pressure, OSAH –
Obstructive Sleep Apnea Hypopnea, AHI – Apnea/Hypopnea Index,
TST – Total Sleep Time, TIB – Time in Bed, WASO – Wake after sleep
onset, SOL – Sleep Onset Latency, SEI – Sleep Efficiency Index
Participants: 20 patients with previously diagnosed OSAH (within
12 months), and successful accommodation to chronic CPAP therapy
at home.
Key Words: sleep-disordered breathing, obstructive sleep apnea -
INTRODUCTION
training, etc.). Patients with non-compliance that is resistant to such
conventional intervention (up to 75%)5 may be placed on Bi-level PAP
therapy to improve compliance. This transition often presents
significant logistic challenges, as many patients are not initially
titrated to both a CPAP and a bi-level prescription. Clinicians may try
empiric initiation with bi-level therapy with BiPAP, but such intervention
must be closely monitored for success or failure.
The prevalence of obstructive sleep apnea – hypopnea syndrome
is estimated to be between 2-4% 1. The disorder remains largely
undiagnosed and under-treated 2. The disorder is associated with an
increased risk of development of psychosocial as well as physiologic
sequela. Effective treatment for the OSAH has been shown to improve
not only directly sleep-related consequences, but the blood pressure
consequences of OSAH 3. Therapy most commonly begins with a
course of continuous positive airway pressure (CPAP). This therapy
has been demonstrated to serve as an effective treatment of the
OSAH syndrome 4.
Reduced compliance reduces physiologic benefits of CPAP therapy.
Strategies to improve compliance have been evaluated, and many
have been implemented in clinical practice (i.e., education, follow-up
contact, heated humidification, etc.). Another factor may be the sensation of high pressure on exhalation. Both conventional CPAP and
Auto-CPAP therapy present elevated pressures during exhalation, and
may be a reason for similar compliance rates for the two applications.
Patients who have demonstrated persistent non-compliance to CPAP
therapy may receive a program of compliance improvement
techniques (i.e., reassessment, counseling, mask fitting, behavioral
hypopnea syndrome, BiPAP therapy, Automatic BiPAP, Bi-level,
Bi-Flex.
BiPAP with Bi-Flex offers a unique form of bi-level therapy by which
Bi-Flex provides flow-directed modification to the transition into and
out of the IPAP phase, and dynamic expiratory pressure relief5. The
amount of expiratory pressure relief is determined by the patient’s
expiratory flow. Accordingly, the pressure returns to therapeutic levels
prior to the initiation of the next breath’s inspiratory phase. The
pressure relief offers a more comfortable expiratory experience for the
patient, and may impact favorably on perceptions of therapy as well as
potentially long-term acceptance to therapy.
Automatically titrating CPAP therapy (Auto-CPAP) has been shown to
effectively treat patients with OSAH 6. Auto-CPAP may be used when
access to titration is limited or to re-titrate patients in whom there are
questions about the effectiveness of their current therapy level.
Further, Auto-CPAP can be used to treat patients with highly variable
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pressure requirements (e.g., REM-related or body-position dependent
OSA)7. These Auto-CPAP algorithms have been employed in a new
BiPAP device. By offering an Auto BiPAP alternative in this case,
extensive re-titration and follow-up empiric pressure modification may
be avoided.
This study was performed to provide a series of basic validations for
the new BiPAP Auto with Bi-Flex technology. The study was to
determine if the therapy would provide adequate resolution to the
underlying OSAH. The BiPAP Auto with Bi-Flex was compared to
conventional manually titrated BiPAP therapy to also evaluate the
ability of the new technology to offer clinicians both a meaningful
‘fixed-CPAP’ therapy pressure as well as a reliable AHI.
METHODS
Twenty chronic CPAP patients were recruited for this study. Subjects
with polysomnographically-determined OSAH and with demonstrated
successful compliance to CPAP therapy were approached for
participation. The research was approved by an Institutional Review
Board, and all subjects gave written, informed consent.
Patients underwent three nights of PSG, scheduled no more than ten
nights apart. Subjects used their current interface (i.e., nasal mask)
and were prepared for standard polysomnography (PSG) for a titration
study. PSG measures included evaluation of sleep state (central
and occipital electroencephalogram, electro-oculogram, sub-mental
electromyogram), respiration (chest and abdominal respiratory effort,
respiratory airflow, and pulse oximetry), body position, ECG, leg
EMG, snoring, and technician comments. Therapy for all nights was
provided by the BiPAP® Pro 2 with Bi-Flex® (Respironics, Inc.,
Murrysville, PA). Device therapy data were recorded on the PSG from
the therapy device (device pressure, flow, and breathing events) via
the Analog Output Module (Respironics, Inc., Murrysville, PA). Patients
were studied in an attended, conventional clinical sleep lab setting.
On the first night, subjects were randomized to either a manual bi-level
positive airway pressure therapy titration or to therapy titration using
the BiPAP Auto with Bi-Flex.
On the manual titration night, pressures were adjusted by an experienced sleep technologist to eliminate obstructive apnea events,
hypopneas and snoring. EPAP and IPAP were maintained between 4
and 25 cm H2O for each patient. The principal investigator determined
the optimal IPAP and EPAP pressures which were to be used on the
fixed therapy pressure night. If the patient had the auto-titration PSG
prior to the manual titration PSG, the principal investigator was
blinded to the results of the BiPAP Auto with Bi-Flex PSG.
On the BiPAP Auto with Bi-Flex titration night, the auto-titrating
algorithm was activated and the device treated the patient with
minimal interference from the sleep technologist. During Auto Bi-level
therapy, EPAP and IPAP were set between 4 and 25 cm H2O for each
patient. The IPAP and EPAP difference (i.e., Pressure Support) was set
at a minimum of 2 cm H2O and a maximum of 8 cm H2O. For savvy
patients who are already accustomed to higher CPAP therapy
and who experienced sleep onset delay due to intolerance of lower
pressure, there was a one-time manual intervention to allow the
subject to initiate sleep with a higher EPAP pressure.
On the third night (Fixed Pressure Night), patients were treated for the
entire night at the optimal bi-level pressure that was determined on
the previous manual titration night at the pressures determined by the
principal investigator using the sleep laboratory’s standard protocol for
bi-level pressure titration.
The PSG studies were then manually scored, using standard scoring
criteria for both sleep state8 and respiratory events9. A standard PSG
report was generated for each sleep study. Pressure data from the
device were recorded on a separate PC.
The statistical approach was based on a null hypothesis so that any
significant differences could be attributed to differences between the
auto-titrating and fixed pressure PSG nights. As each subject served
as his/her own control, comparisons were made using a paired t-test
(MedCalc software, Version 7.5; Belgium), examining for differences in
major variables of sleep duration, sleep stage, sleep continuity,
arousals from sleep, and AHI. Comparisons were made between the
best pressure on the manual titration night and the 90% pressure
determined using the BiPAP Auto with Bi-Flex in the Auto Bi-level
mode. Post-hoc analyses focused on differences between the AHI
at the time of initial presentation of the patient and the titration
pressures determined on the two nights.
RESULTS
Demographics
The twenty subjects (5 female, 15 male) had a mean age of 56 ± 9
years. Other demographic characteristics are presented in Table 1.
Nineteen of the twenty patients were using CPAP prior to entering the
study. (Table 1).
Table 1.
Gender
5 female , 15 male
Age (years)
56 ± 9
BMI (kg/m2)
37 ± 6
Diagnostic AHI (hr -1)
41 ± 27
Time Elapsed since
initiating CPAP treatment (days)
196 ± 399
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Sleep Quality
Sleep parameters for each PSG night were analyzed. Subjects slept
a comparable duration during the three study nights. There were no
significant differences in Time in Bed (TIB), Total Sleep Time (TST) in
hours, Sleep Latency, or Sleep Efficiency. Arousal rates were
comparable between all three nights. (See Table 2).
Table 2.
Manual Bi-level
Therapy
Titration
BiPAP Auto
with Bi-Flex
Therapy
Fixed Pressure
Bi-level
Sig.
Therapy
TIB (min)
400.7 ± 30
413.5 ± 23.2
400.2 ± 37
NS
TST (min)
352.4 ± 29
364.4 ± 48
335.1 ± 49
NS
Sleep Onset Latency (min) 6.6 ± 7.3
8.4 ± 12.6
8.0 ± 8.8
NS
Sleep Efficiency (%)
88.1 ± 5.9
87.1 ± 9.6
87.6 ± 8.6
NS
Stage 3/4 Sleep (min)
21.2 ± 25.8
20.8 ± 25.4
14.1 ± 20.6
NS
REM Sleep (min)
60.6 ± 29.5
65.9 ± 35.5
63.7 ± 33.3
NS
Arousal Index (hr-1)
25.6± 33.3
15.8 ± 8.4
14.4 ± 9.7
NS
Figure 1 shows the relationship between residual AHI from the
manually titrated bi-level night, and the BiPAP Auto with Bi-Flex night.
There is a good correlation between the two titration methodologies.
Figure 1.
AHI- Manual Titration Night vs. BiPAP Auto with Bi-Flex Night
BiPAP Auto with Bi-Flex Night
165XX Respcs Auto Bi-PAP WP
Manual Titration Night
Figure 2 is a Bland-Altman plot comparing the AHI from the
manually titrated bi-level night and the BiPAP Auto with Bi-Flex night.
Figure 2.
Bland & Altman Plot – AHI Auto vs. AHI Manual
Residual AHI, apnea index and hypopnea index were comparable
between the titration nights. No significant differences were seen in
minimum oxygen saturation (Table 3).
Difference/Mean
THERAPY PERFORMANCE
Table 3.
Mean
Manual Bi-level
Therapy
Titration
BiPAP Auto
with Bi-Flex
Therapy
Fixed Pressure
Bi-level
Sig.
Therapy
Residual AHI (hr-1)
4.5 ± 3.9
3.2±2.8
2.9± 3.6
NS
Apnea Index (hr-1)
1.3 ± 1.5
0.9 ± 1.2
1.2 ± 1.9
NS
Hypopnea Index (hr-1)
3.2 ± 3.1
2.3 ± 2.0
1.6 ± 2.5
NS
Figure 3
Min SpO2 (%)
89.5±3.1
89.9±2.9
89 ± 8.2
NS
AHI- Fixed Bi-level Pressure Night vs. BiPAP Auto with Bi-Flex Night
BiPAP Auto with Bi-Flex Night
Figure 3 shows the BiPAP Auto with Bi-Flex residual AHI vs. the fixed
pressure night residual AHI.
Fixed Bi-level Pressures Night
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Figure 4 shows the Bland-Altman plot for BiPAP Auto with Bi-Flex
residual AHI vs. the fixed pressure night residual AHI.
Figure 4.
Difference of corresponding AHI's
Bland & Altman Plot – AHI Auto vs. AHI Fixed
The mean, average IPAP pressure (determined for the entire night by
the auto algorithm) was significantly lower than the average, manual
titration IPAP (determined during manual titration) (p < 0.001). The
average, maximum IPAP pressure (determined by the BiPAP Auto
with Bi-Flex during the auto-titration night) was significantly higher
than the device determined mean, average IPAP (the mean value of
IPAP for the entire night determined by the auto algorithm)
(p< 0.001). The average maximum IPAP pressure trended to be higher compared to the average 90% IPAP pressure but barely failed to
be significant (p = 0.053).
Table 4.
Manually
Titrated
IPAP
Pressure
Fixed
Pressure
IPAP
Pressure
BiPAP
Auto with
Bi-Flex
Therapy
Average
IPAP
Pressure
BiPAP
Auto with
Bi-Flex
Therapy
90% IPAP
Pressure
BiPAP
Auto with
Bi-Flex
Therapy
Maximum
IPAP
Pressure
Mean
12.9*
12.5
9.8**
12.0
13.9**
SD
2.9
2.9
2.7
3.6
3.6
Mean of corresponding AHI's
These data demonstrate that the BiPAP Auto with Bi-Flex achieves
therapy efficacy comparable to that achieved with manual titration and
during manually titrated fixed pressure bi-level therapy. No significant
differences were seen between BiPAP Auto with Bi-Flex and the
other nights with regards to sleep parameters and amelioration of
breathing events.
p value (ANOVA)
0.002
* p < 0.001, Manually Titrated IPAP compared to average IPAP
** p < 0.001, Average IPAP compared to maximum IPAP
THERAPY PRESSURE COMPARISON
IPAP Analysis
Figure 5 illustrates the IPAP pressures from the manual titration night,
the fixed pressure night and the 90% pressure, the highest pressure,
and the average pressure from the auto-titration night.
Figure 5. (IPAP mean values)
IPAP Pressure
An initial analysis using ANOVA revealed significant differences
between the IPAP mean values (p = 0.002). (Table 4)
These data demonstrate that the BiPAP Auto with Bi-Flex algorithm
determines IPAP pressure in a manner similar to manually titrated
IPAP pressure. Although the algorithm determined highest pressure
was higher than the manually titrated IPAP pressure, the average
IPAP pressure was significantly lower than the manually titrated, best
(or the IPAP pressure that would have been prescribed) IPAP.
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EPAP ANALYSIS
DISCUSSION
Figure 6 illustrates the EPAP pressures from the manual titration
night, the fixed pressure night and the 90% pressure, the highest
pressure, and the average pressure from the auto-titration night.
The ability of the BiPAP Auto with Bi-Flex in the auto-titrating mode
to reduce obstructive apnea and hypopnea as effectively as manually
adjusted bi-level positive airway pressure titration is demonstrated in
this subject set. With very low residual AHI’s, the BiPAP Auto with
Bi-Flex meets accepted criteria for therapeutic success10. The BiPAP
Figure 6. (EPAP mean values)
Auto with Bi-Flex provided comparable therapy as compared to
manually titrated, Bi-level positive airway pressure.
EPAP Pressure
The average IPAP pressure value over the entire night was
significantly lower than the average IPAP on either the manual
titration night or the fixed pressure night. The highest IPAP pressure
deemed necessary by the auto-titrating algorithm was not
significantly different from the manual titration or the fixed pressure
IPAP. The EPAP pressures did not differ significantly between any of
the therapeutic modes. As is seen with auto-titrating CPAP devices,
therapeutic efficacy is achieved with lower pressures on average.
The duration of sleep and sleep architecture for the three nights were
similar. Patients on BiPAP Auto with Bi-Flex had sleep that was
similar to that experienced during a comparable in-laboratory titration
on two separate therapy nights. This indicates that auto-titrating
bi-level positive airway pressure with Bi-Flex does not negatively
affect sleep quality.
Table 5 presents the analysis of the mean EPAP values from each
PSG night.
Table 5.
Manual
Best Rx
EPAP
Pressure
Fixed
Pressure
EPAP
Pressure
BiPAP
Auto
with
Bi-Flex
Therapy
Titrating
Average
EPAP
Pressure
BiPAP
Auto
with
Bi-Flex
Therapy
Titrating
90% EPAP
Pressure
BiPAP
Auto
with
Bi-Flex
Therapy
Titrating
Maximum
EPAP
Pressure
Mean
9.3
9.0
7.0
9.0
9.8
SD
3.2
3.3
2.7
3.7
3.8
p value (ANOVA)
NS
Using ANOVA, no significant differences were revealed between any
of the EPAP pressures although the mean, average EPAP pressure
(the average EPAP for the entire night determined by the device)
trended to be lower than the other EPAP pressure values.
Consequences of the apnea and hypopnea events, arousals and
desaturations, were comparable during use of the BiPAP Auto with
Bi-Flex in the auto-titrating mode night as during the manual titration
and fixed pressure nights.
In certain medical environments, BiPAP Auto with Bi-Flex may be
utilized in hospitalized or disabled patients as well as those in whom a
re-titration might be indicated because of poor adherence or CPAP
therapy. The ability to offer the patient an alternative pressure profile
from the BiPAP Auto with Bi-Flex device, and determine compliance
changes, are essential for such an application. These data suggest
that the 90% pressure from the BiPAP Auto with Bi-Flex can serve
to reach decisions for setting ‘fixed’ BiPAP with Bi-Flex pressures, if
so desired.
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CONCLUSION
REFERENCES
The BiPAP Auto with Bi-Flex provides effective therapy in this group
of 20 OSAS patients. With the mean residual AHI of less than
5 hr -1 sleep, the BiPAP Auto with Bi-Flex provides adequate clinical
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architecture is comparable to that experienced during manual titration.
BiPAP Auto with Bi-Flex provided therapeutic information (breathing
events, average pressures, 90% inspiratory and expiratory pressures)
comparable to that derived by conventional bi-level titration. This initial
evaluation demonstrates the efficacy of the BiPAP Auto with Bi-Flex
technology as a method to either treat or determine pressure
requirements for patients with obstructive sleep apnea.
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Tested with software version B7.6.
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